Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II.

Human leukocyte antigen (HLA) molecular mismatch is a powerful biomarker of rejection. Few studies have explored its use in assessing rejection risk in heart transplant recipients. We tested the hypothesis that a combination of HLA Epitope Mismatch Algorithm (HLA-EMMA) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) algorithms can improve risk stratification of pediatric heart transplant recipients. Class I and II HLA genotyping were performed by next-generation sequencing on 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC). Using high-resolution genotypes, we performed HLA molecular mismatch analysis with HLA-EMMA and PIRCHE-II, and correlated these findings with clinical outcomes. Patients without pre-formed donor specific antibody (DSA) (n=100) were used for correlations with post-transplant DSA and antibody mediated rejection (ABMR). Risk cut-offs were determined for DSA and ABMR using both algorithms. HLA-EMMA cut-offs alone predict the risk of DSA and ABMR; however, if used in combination with PIRCHE-II, the population could be further stratified into low-, intermediate-, and high-risk groups. The combination of HLA-EMMA and PIRCHE-II enables more granular immunological risk stratification. Intermediate-risk cases, like low-risk cases, are at a lower risk of DSA and ABMR. This new way of risk evaluation may facilitate individualized immunosuppression and surveillance.

The influence of mechanical Circulatory support on post-transplant outcomes in pediatric patients: A multicenter study from the International Society for Heart and Lung Transplantation (ISHLT) Registry.

BACKGROUND: Mechanical circulatory support (MCS) is increasingly being used as a bridge to transplant in pediatric patients. We compare outcomes in pediatric patients bridged to transplant with MCS from an international cohort. METHODS: This retrospective cohort study of heart-transplant patients reported to the International Society for Heart and Lung Transplantation (ISHLT) registry from 2005-2017 includes 5,095 patients <18 years. Pretransplant MCS exposure and anatomic diagnosis were derived. Outcomes included mortality, renal failure, and stroke. RESULTS: 26% of patients received MCS prior to transplant: 240 (4.7%) on extracorporeal membrane oxygenation (ECMO), 1,030 (20.2%) on ventricular assist device (VAD), and 54 (1%) both. 29% of patients were <1 year, and 43.8% had congenital heart disease (CHD). After adjusting for clinical characteristics, compared to no-MCS and VAD, ECMO had higher mortality during their transplant hospitalization [OR 3.97 & 2.55; 95% CI 2.43-6.49 & 1.42-4.60] while VAD mortality was similar [OR 1.55; CI 0.99-2.45]. Outcomes of ECMO+VAD were similar to ECMO alone, including increased mortality during transplant hospitalization compared to no-MCS [OR 4.74; CI 1.81-12.36]. Patients with CHD on ECMO had increased 1 year, and 10 year mortality [HR 2.36; CI 1.65-3.39], [HR 1.82; CI 1.33-2.49]; there was no difference in survival in dilated cardiomyopathy (DCM) patients based on pretransplant MCS status. CONCLUSION: Survival in CHD and DCM is similar in patients with no MCS or VAD prior to transplant, while pretransplant ECMO use is strongly associated with mortality after transplant particularly in children with CHD. In children with DCM, long term survival was equivalent regardless of MCS status.

Characteristics and outcomes of AED use in pediatric cardiac arrest in public settings: The influence of neighborhood characteristics.

BACKGROUND: Automated external defibrillators (AEDs) are critical in the chain of survival following out-of-hospital cardiac arrest (OHCA), yet few studies have reported on AED use and outcomes among pediatric OHCA. This study describes the association between bystander AED use, neighborhood characteristics and survival outcomes following public pediatric OHCA. METHODS: Non-traumatic OHCAs among children less than18 years of age in a public setting between from January 1, 2013 through December 31, 2017 were identified in the CARES database. A neighborhood characteristic index was created from the addition of dichotomous values of 4 American Community Survey neighborhood characteristics at the Census tract level: median household income, percent high school graduates, percent unemployment, and percent African American. Multivariable logistic regression models assessed the association of OHCA characteristics, the neighborhood characteristic index and outcomes. RESULTS: Of 971 pediatric OHCA, AEDs were used by bystanders in 10.3% of OHCAs. AEDs were used on 2.3% of children ≤1 year (infants), 8.3% of 2-5 year-olds, 12.4% of 6-11 year-olds, and 18.2% of 12-18 year-olds (p < 0.001). AED use was more common in neighborhoods with a median household income of >$50,000 per year (12.3%; p = 0.016), <10% unemployment (12.1%; p = 0.002), and >80% high school education (11.8%; p = 0.002). Greater survival to hospital discharge and neurologically favorable survival were among arrests with bystander AED use, varying by neighborhood characteristics. CONCLUSIONS: Bystander AED use is uncommon in pediatric OHCA, particularly in high-risk neighborhoods, but improves survival. Further study is needed to understand disparities in AED use and outcomes.